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初步研究丙戊酸治疗的癫痫患者铜供应减少与非酒精性脂肪性肝病之间的可能关联。

A preliminary investigation on the possible association between diminished copper availability and non-alcoholic fatty liver disease in epileptic patients treated with valproic acid.

机构信息

Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.

出版信息

Ups J Med Sci. 2011 May;116(2):148-54. doi: 10.3109/03009734.2010.545898. Epub 2010 Dec 29.

Abstract

BACKGROUND

Patients treated with valproic acid (VPA) present a high incidence of non-alcoholic fatty liver disease (NAFLD) (around 61%). Several recent studies suggest that low copper stores could be associated with NAFLD, and a significant decrease of copper availability in VPA-treated patients has been described.

DESIGN AND METHODS

In 101 adult epileptic patients treated with valproic acid in monotherapy (n = 75) and polytherapy (n = 26) the copper availability was evaluated using the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) and the copper/ceruloplasmin ratio. Copper deficiency was supposed in the cases in which this biochemical variable was smaller than the lower reference limit (333 U/g).

RESULTS

The differences between the groups of patients with ceruloplasmin oxidase activity smaller or greater than 333 U/g for the serum levels of aminotransferases, gamma-glutamyltransferase, butyrylcholinesterase, cholesterol, triglycerides, and C-reactive protein, and the APRI and FIB-4 liver fibrosis scores were not statistically significant. Most patients (93%) had low APRI and FIB-4 scores, suggesting absence of significant liver fibrosis.

CONCLUSIONS

The results obtained do not confirm the hypothesis of an association between diminished copper availability and NAFLD in patients treated with valproic acid.

摘要

背景

接受丙戊酸(VPA)治疗的患者患有非酒精性脂肪性肝病(NAFLD)的发病率很高(约 61%)。最近的几项研究表明,低铜储存量可能与 NAFLD 有关,并且已经描述了 VPA 治疗患者的铜供应显著减少。

设计和方法

在 101 名接受丙戊酸单药治疗(n=75)和联合治疗(n=26)的成年癫痫患者中,使用铜蓝蛋白的特异性氧化酶活性(单位质量酶蛋白的活性)和铜/铜蓝蛋白比值来评估铜的可用性。假设当这种生化变量小于下参考限(333 U/g)时,存在铜缺乏。

结果

对于血清转氨酶、γ-谷氨酰转移酶、丁酰胆碱酯酶、胆固醇、甘油三酯和 C 反应蛋白的水平,以及 APRI 和 FIB-4 纤维化评分,具有小于或大于 333 U/g 血清铜蓝蛋白氧化酶活性的患者组之间的差异无统计学意义。大多数患者(93%)的 APRI 和 FIB-4 评分较低,表明不存在明显的肝纤维化。

结论

所获得的结果不支持铜供应减少与接受丙戊酸治疗的患者的 NAFLD 之间存在关联的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33fe/3078546/f8b1ed9df0b7/UPS-0300-9734-116-148_g001.jpg

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